Our purposeWe enable people with life-altering conditions to lead better lives.

Innovation

Exane BNP Paribas 14th Healthcare Conference

10th May 2012

Sylvie GrégoirePresident, Human Genetic Therapies

To be as brave as the people we help.

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The Start of Our Journey: Shire’s First Headquarters (1988)

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Transformation continues

2004

• ADDERALL XR and ADHDthe prime focus

• Small molecules• Oral drug delivery (SLI)• Hatch Waxman dependent• US the dominant market• Presence in Canada and

6 EU markets

2012

• Leading Specialty Biopharmaceutical Company

• Business based on:• Small molecules• Peptides• Biologics

• Technology platforms• Human cell line biologics• Carrier Wave• Locked Nucleic Acid Technology

• ADHD, GI, HGT and Regenerative Medicine• Balanced product portfolio

• Products with global rights• Strong pipeline• Robust Intellectual property• Presence in 29 countries and growing

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Global Expansion and Some Success (2012)

Lexington, MA

Basingstoke, UK

Chesterbrook, PA

Nyon, Switzerland

71%

68%

5%Sao Paolo, Brazil San Diego, CA

2012 Eurordis Company AwardExemplary work in the field of rare diseases

2011 Company of the Year (2nd year)European Medicine Awards

2011 ISPE Facility of the Year AwardHonorable Mention

Named one of the top women-led businesses in Massachusetts (2011)

Named one of Massachusetts High Tech’s “Tech Citizens” for

our philanthropic work (2010)

2010 UK Prix Galien award for FIRAZYR

2010 Partners in Progress Award for Accelerated Development of VPRIV

National Organization for Rare Disorders (NORD)

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Shire HGT has an Extensive Global Footprint: Direct Presence in 29 Countries with Sales in 48

Direct PresenceKey Partner Distribution Sites

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Human Genetic Therapies (HGT)Orphan Diseases

Specialty Pharmaceuticals (SP)Attention Deficit Hyperactivity Disorder (ADHD) ,

Gastrointestinal (GI), Renal, Hematology

Advanced BioHealing (ABH)Regenerative Medicine

Shire: Three Decentralized BusinessesFocus on symptomatic diseases and individual patient needs is key to Shire’s success

Acquisition of ABH adds a strategic platform in Regenerative Medicine

Vascugel®

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KEYPRODUCTS

LATE STAGE PIPELINE

EARLY STAGE PIPELINEVALIDATING TECHNOLOGY PLATFORMS

RESOLOR

LIALDA

VYVANSE

ELAPRASE

REPLAGAL

VPRIV

INTUNIV

FIRAZYR

DERMA-GRAFT

VYVANSEEx-US

Investing to deliver growth now and into the future, supported by strong cash generation

VYVANSEMDDVYVANSE

BED

INTUNIVEx-US

Specialty PharmaVYVANSE NSS&EDS

CarrierwaveHematology

Movetis assets

HGT Hunter CNSSanfilippo ASanfilippo B

DMDMLD

Emer

ging

Res

earc

h As

sets

SPD602IRON

OVERLOADRMVASCUGELRegen Med

assets

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NMEs per $B R&D spent (inflation adjusted)

Structure of DNA

Restrictionenzymes

DNA sequencing

RecombinantDNA

Humaninsulin

Dolly theSheep

Humangenome v1

0.1

1

10

100

1950 1960 1970 1980 1990 2000 2010

Note: R&D costs are estimated from PhRMA annual survey 2009; NMEs are the total number of small molecule and biologic approvals by the FDASource: Bernstein Research “The Long View – R&D Productivity” (September 30, 2010), Source Boston Consulting Group

Pharma R&D Productivity Consistently Declining:A Broken Business Model

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Charles Darwin

It is not the strongest of the species that survives, nor the most intelligent that survives. It is the one that is the most adaptable to change.

“

”

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Delivering Value in a Challenging Environment

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Our Core Focus

Profoundly impacting the lives of patients who suffer from devastating rare diseases

Provide financial return to shareholders

Clearly address the rapidly changing needs of stakeholders in the Circle of Value

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R&D as an Engine of Growth and Change

Time

Gro

wth

Time

Gro

wth

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Research-Process Development Partnership: Joint Accountability to Deliver Therapies More Quickly

Knowledge

Time

Early Development

Process Development

Knowledge

Time

Early Development

Process Development

Partnering

Over The Fence

Discovery

Discovery

Transition

Transition

• Less duplication• Faster• Consistency• Flexibility• Reduced risk• Leverage resources for

new tech platforms• Co-location of Res and

PD personnel

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• Increased intensity of focus on vendor management• Align incentives• Demand high quality and performance from vendors

• Nimbler internal processes• Speed of decision-making• Enhanced partnership with procurement

• Leverage increasing scale• Relationships across HGT, SP, ABH• Establish global strategies (e.g. for clinical studies)

• Preferred relationships• Opportunities for broad commitments with the right suppliers

• Creativity• New models which align with key strategic needs• Social networking

New Supplier Relationships

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Innovation and Creativity Focused on Business Needs

• Creative Preclinical and Clinical Science

• Creative engagement of Regulatory authorities

• Creative external partnerships

• Creative ways to decrease time to approval

• Creative partnerships within Shire

• Creative people development opportunities

• Create value to Payers

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Creativity Focused on Business Needs: Intrathecal Technology

• Challenge Paradigms

• Apply Technology In New Ways

• New Business Relationships

• Profound Impact OnCurrent and New Patients

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Creativity Focused on Business Needs:Manufacturing Technology

• Challenge Paradigms

• Apply Technology In New Ways

• New Business Relationships

• Profoundly Impact OnCurrent and New Patients

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To be as brave as the people we help.

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Creative External Partnerships: Alliance with Atlas Venture

We recently announced that R&D has formed an alliance with Atlas Venture

Objective• To identify and invest in early-stage companies formed around single assets for which

Shire will retain an exclusive optionScope• Rare disease therapeuticsAdvantage• Combining Atlas Venture’s entrepreneurial network and experience in new company

formation with HGT’s expertise in rare disease research, development, and commercialization

We believe that multiple investments across project-focused companies will mitigate early-stage development risk

Retaining rights to acquire these assets after de-risking allows for expansion of the pipeline while maintaining organizational flexibility

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Creative External Partnerships:Strategic Investment Group (SIG)

Focusing on the diagnosis and treatment of food allergies such as peanut and milk allergies. DBV Technologies’ novel approach to food allergy diagnosis and treatment is focused on eliciting an immune response by targeting antigen to the skin epidermis. The antigens (allergens) are delivered to the skin using DBV Technologies’ unique worldwide patented delivery system, VIASKIN®www.dbvtechnologies.com

Advancing treatment of neurodegenerative diseases through a novel approach to disaggregating proteins using plaque technology. NPT001, the lead molecule, has been shown in animal models to disaggregate amyloidplaques.www.neurophage.com

Prexa develops proprietary oral small molecule therapeutics targeting treatment of neuropsychological disorders. Prexa’s proprietary chemistry approach is focused on discovery of highly differentiated tri-reuptake inhibitors with unique dopamine-biased neurotransmitter transport selectivity profiles and rationally designed CNS PK. Prexa is also testing mono- and di-reuptake inhibitors for activity in ADHD animal models.www.adventhealthcareventures.com/prexa

Naurex Inc. is a clinical-stage company developing novel therapies for depression and other CNS disorders based on a new mechanism of action for modulating the N-methyl-D-aspartic acid receptor (NMDAR). Using these discoveries, Naurex researchers have generated novel chemical drug classes known as glycine-site functional partial agonists (GFPAs), which modulate the receptor in a different way than existing NMDAR agents. The company’s drug development programs include the first-generation molecule, GLYX-13, the second-generation NRX-1050 small molecule series and additional compounds from Naurex’s platform of novel NMDAR modulators. www.naurex.com

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Creative External Engagement:Social Networking

• Patient recruitment through CRO’s• Patient education• Patient engagement (e.g. patientslikeme)• Internal Shire engagement• Problem solving (e.g. exploring open innovation with Harvard)• ………

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Delivering Value in a Challenging Environment

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Balanced product portfolio provides foundation for future growth

Delivering good revenue and earnings growth

Demonstrating value to stakeholders in a changing healthcare environment

Expanding the pipeline through new acquisitions and partnerships